Advertisement
Platinum Priority – Prostate Cancer Editorial by Behfar Ehdaie and Karim A. Touijer on pp. 788–789 of this issue| Volume 63, ISSUE 5, P779-787, May 01, 2013

Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised, Placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS)

Published:November 14, 2012DOI:https://doi.org/10.1016/j.eururo.2012.11.006

      Abstract

      Background

      Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.

      Objective

      To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.

      Design, setting, and participants

      Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.

      Intervention

      The 5α-reductase inhibitor, dutasteride.

      Outcome measurements and statistical analysis

      The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.

      Results and limitations

      Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35–76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.

      Conclusions

      Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.

      Clinical trial registry

      ClinicalTrials.gov, NCT00558363.

      Keywords

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to European Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Makarov D.V.
        • Trock B.J.
        • Humphreys E.B.
        • et al.
        Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin tables) based on cases from 2000 to 2005.
        Urology. 2007; 69: 1095-1101
        • Heidenreich A.
        • Aus G.
        • Bolla M.
        • et al.
        EAU guidelines on prostate cancer.
        Eur Urol. 2008; 53: 68-80
        • Pound C.R.
        • Partin A.W.
        • Eisenberger M.A.
        • Chan D.W.
        • Pearson J.D.
        • Walsh P.C.
        Natural history of progression after PSA elevation following radical prostatectomy.
        JAMA. 1999; 281: 1591-1597
        • Schröder F.H.
        • Bangma C.H.
        • Wolff J.M.
        • et al.
        Can dutasteride delay or prevent the progression of prostate cancer in patients with biochemical failure after radical therapy? Rationale and design of the Avodart After Radical Therapy for Prostate Cancer Study.
        BJU Int. 2009; 103: 590-596
        • Roach III, M.
        • Hanks G.
        • Thames Jr., H.
        • et al.
        Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.
        Int J Radiat Oncol Biol Phys. 2006; 65: 965-974
        • Molitierno J.
        • Evans A.
        • Mohler J.L.
        • Wallen E.
        • Moore D.
        • Pruthi R.S.
        Characterization of biochemical recurrence after radical prostatectomy.
        Urol Int. 2006; 77: 130-134
        • Lee W.R.
        • Hanks G.E.
        • Hanlon A.
        Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations.
        J Clin Oncol. 1997; 15: 230-238
        • Scher H.I.
        • Eisenberger M.
        • D’Amico A.V.
        • et al.
        Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group.
        J Clin Oncol. 2004; 22: 537-556
        • Patel A.
        • Dorey F.
        • Franklin J.
        • deKernion J.B.
        Recurrence patterns after radical retropubic prostatectomy: clinical usefulness of prostate specific antigen doubling times and log slope prostate specific antigen.
        J Urol. 1997; 158: 1441-1445
        • Zagars G.K.
        • Pollack A.
        Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer.
        Radiother Oncol. 1997; 44: 213-221
        • Evans H.C.
        • Goa K.L.
        Dutasteride.
        Drugs Aging. 2003; 20: 905-916
        • Goluboff E.T.
        • Prager D.
        • Rukstalis D.
        • et al.
        • UCLA Oncology Research Network
        Safety and efficacy of exisulind for treatment of recurrent prostate cancer after radical prostatectomy.
        J Urol. 2001; 166: 882-886
        • Smith M.R.
        • Manola J.
        • Kaufman D.S.
        • et al.
        Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy.
        Cancer. 2004; 101: 1569-1574
        • Smith M.R.
        • Manola J.
        • Kaufman D.S.
        • Oh W.K.
        • Bubley G.K.
        • Kantoff P.W.
        Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy.
        J Clin Oncol. 2006; 24: 2723-2728
        • Schröder F.H.
        • Roobol M.J.
        • Boevé E.R.
        • et al.
        Randomized, double-blind, placebo-controlled crossover study in men with prostate cancer and rising PSA: effectiveness of a dietary supplement.
        Eur Urol. 2005; 48: 922-931
        • Marschner N.
        • Rüttinger D.
        • Zugmaier G.
        • et al.
        Phase II study of the human anti-epithelial cell adhesion molecule antibody adecatumumab in prostate cancer patients with increasing serum levels of prostate-specific antigen after radical prostatectomy.
        Urol Int. 2010; 85: 386-395
        • Andriole G.
        • Lieber M.
        • Smith J.
        • et al.
        Treatment with finasteride following radical prostatectomy for prostate cancer.
        Urology. 1995; 45: 491-497
        • Montorsi F.
        • Alcaraz A.
        • Desgrandchamps F.
        • Hammerer P.
        • Schröder F.
        • Castro F.
        A broader role for 5ARIs in prostate disease? Existing evidence and emerging benefits.
        Prostate. 2009; 69: 895-907
        • Albertsen P.C.
        • Hanley J.A.
        • Penson D.F.
        • Fine J.
        Validation of increasing prostate-specific antigen as a predictor of prostate cancer death after treatment of localized prostate cancer with surgery or radiation.
        J Urol. 2004; 171: 2221-2225
        • D’Amico A.V.
        • Moul J.W.
        • Carroll P.R.
        • Sun L.
        • Lubeck D.
        • Chen M.H.
        Surrogate end point for prostate cancer-specific mortality after radical prostatectomy or radiation therapy.
        J Natl Cancer Inst. 2003; 95: 1376-1383
        • Teeter A.E.
        • Presti Jr., J.C.
        • Aronson W.J.
        • et al.
        Does PSADT after radical prostatectomy correlate with overall survival? A report from the SEARCH database group.
        Urology. 2011; 77: 149-153
        • Freedland S.J.
        • Humphreys E.B.
        • Mangold L.A.
        • et al.
        Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy.
        JAMA. 2005; 294: 433-439
        • Freedland S.J.
        • Humphreys E.B.
        • Mangold L.A.
        • et al.
        Death in patients with recurrent prostate cancer after radical prostatectomy: prostate-specific antigen doubling time subgroups and their associated contributions to all-cause mortality.
        J Clin Oncol. 2007; 25: 1765-1771